MicroRNAs Provide Feedback Regulation of Epithelial-Mesenchymal Transition Induced by Growth Factors
MicroRNAs Provide Feedback Regulation of Epithelial-Mesenchymal Transition Induced by Growth Factors
复制标题
MicroRNA 对生长因子诱导的上皮间质转化提供反馈调节
DOI：
10.1002/jcp.25060
复制
发表时间：
2016-01-01
影响因子：
5.6
通讯作者：
Ma, Jian
中科院分区：
文献类型：
--
作者：
Qin, Zailong;He, Wei;Ma, Jian
microRNA作为基因表达调控因子，参与细胞分化、凋亡、细胞周期、上皮细胞向间质细胞转化（EMT）等多种生物学过程。为了探讨它们在EMT过程中的作用，我们分析了EGF和TGF-β诱导的鼻咽癌细胞HK-1 microRNA表达谱的变化，发现miR-21、miR-148 a、miR-505和miR-1207- 5 p在生长因子诱导的EMT过程中表达上调。miR-21是已知的促进肿瘤转移的致癌miRNA，但其他三种miRNA在EMT中的确切功能尚不清楚。我们发现miR-148 a、miR-505和miR-1207- 5 p在体内外均能抑制HK-1细胞的EMT和转移表型，这可能与它们抑制EMT和Wnt信号分子有关。miRNA通过转录后抑制与先前发育阶段或替代细胞命运相关的关键转录程序来赋予生物过程鲁棒性。我们的研究结果表明，miRNA反馈回路被调谐以响应生长因子诱导的EMT，我们提出了一个新的负反馈回路，这可能是EMT过程的重要元素，并赋予生物鲁棒性。J.细胞。Physiol.230：120-129，2016。(c)2015 Wiley Periodicals，Inc.
As regulators in gene expression, microRNAs take part in most biological processes including cell differentiation, apoptosis, cell cycle, and epithelial-to-mesenchymal transition (EMT). In order to evaluate their roles in EMT process, microRNA expression profile changes induced by EGF or TGF- treatment on nasopharyngeal carcinoma cell HK-1 were analyzed, and miR-21, miR-148a, miR-505, and miR-1207-5p were found to be upregulated in growth factors-induced EMT process. miR-21 is already known as an oncogenic miRNA to promote metastasis, however, the exact functions of other three miRNAs in EMT are unclear. To our surprise, we found that miR-148a, miR-505, and miR-1207-5p can suppress EMT and metastasis phenotypes in HK-1 cells both in vitro and in vivo, which may relate to their inhibition on EMT and Wnt signaling molecules. MiRNAs confer robustness to biological processes by posttranscriptional repression of key transcriptional programs that are related to previous developmental stages or to alternative cell fates. Our findings indicate that miRNA feedback circuit is tuned to respond to growth factors-induced EMT, and we suggested a new negative feedback loop which may be an important element of the EMT process and confer biological robustness. J. Cell. Physiol. 230: 120-129, 2016. (c) 2015 Wiley Periodicals, Inc.